To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Coronavirus disease 2019 (COVID-19) spread globally, including across Europe, resulting in different morbidity and mortality outcomes. The aim of this study was to explore the progression of the COVID-19 pandemic over 18 mo in relation to the effect of COVID-19 vaccination at a population level across 35 nations in Europe, while evaluating the data for cross-border epidemiological trends to identify any pertinent lessons that can be implemented in the future.
Epidemiological data were obtained from European Centre for Disease Prevention and Control and Our World in Data databases while Ministry of Health websites of each respective country and local newspapers were used for COVID-19-related vaccination strategies. Case, mortality, and vaccination incidence comparative analyses were made across neighboring countries.
Similar morbidity and mortality outcomes were evident across neighboring countries over 18 mo, with a bidirectional relationship evident between cumulative fully vaccinated population and case fatality rates.
Countries’ COVID-19 outcome is related on national mitigative measures, vaccination rollouts, and neighboring countries’ actions and COVID-19 situations. Mass population vaccination appeared to be effective in reducing COVID-19 case severity and mortality rates. Vaccination equity and pan-European commitment for cross-border governance appear to be the way forward to ensure populations’ return to “normality.”
ABSTRACT IMPACT: Genomic variation likely plays a role in differences in rates of adverse reactions and efficacy for African populations, and this research will add to the understudied field of pharmacogenomics in African populations. OBJECTIVES/GOALS: We aim to characterize the frequency of variants in clinically relevant genes in East and West African populations to assess the prevalence of potential drug-gene interactions. METHODS/STUDY POPULATION: Our pilot study will consist of 100 Somali patients enrolled at Mayo Clinic Rochester and 100 Ghanaian patients recruited at Teaching Hospitals in Ghana. Germline DNA will be extracted from pre-existing blood samples. Sequencing will be performed using Admera Health’s PGxOne Plus test, interrogating a panel of 62 genes. Variants will be reported along with the predicted response for a list of drugs. Differences between frequencies of variants in East and West African populations will be analyzed. We will look for correlations with reported adverse reaction rates. We will then compare our findings with allele frequency data from publicly available data bases. Additionally, we will analyze the flanking regions of the panel for novel variants, using machine learning to predict gene-drug interactions. RESULTS/ANTICIPATED RESULTS: African populations are known to have more genetic diversity than any other population. Additionally, only African-Americans, African-Caribbeans from Barbados, Esan and Yoruba Nigerians, Gambians, Kenyans, and Sierra Leoneans are accounted for within the publicly available data bases most often used for variant studies. Thus, it is anticipated that we will find differences in the variant allele frequencies of our populations compared to European allele frequencies, and differences in frequencies between the East and West African populations. In the 200 base pair flanking regions that are sequenced in the assay along with the known variant regions, we may find novel previously unreported variants. DISCUSSION/SIGNIFICANCE OF FINDINGS: The lack of knowledge of pharmacogenomic variation in African populations contributes to ethnic disparities in patient outcomes. This study addresses this gap by adding to our comprehension of variants in clinically relevant genes, giving insight into underlying mechanisms of ethnicity-based drug responses.
Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction.
Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression. Here, we explore the use of a simulation centre environment in evaluating the usability of Aifred, particularly its impact on the physician–patient interaction.
Twenty psychiatry and family medicine attending staff and residents were recruited to complete a 2.5-h study at a clinical interaction simulation centre with standardised patients. Each physician had the option of using the CDSS to inform their treatment choice in three 10-min clinical scenarios with standardised patients portraying mild, moderate and severe episodes of major depression. Feasibility and acceptability data were collected through self-report questionnaires, scenario observations, interviews and standardised patient feedback.
All 20 participants completed the study. Initial results indicate that the tool was acceptable to clinicians and feasible for use during clinical encounters. Clinicians indicated a willingness to use the tool in real clinical practice, a significant degree of trust in the system's predictions to assist with treatment selection, and reported that the tool helped increase patient understanding of and trust in treatment. The simulation environment allowed for the evaluation of the tool's impact on the physician–patient interaction.
The simulation centre allowed for direct observations of clinician use and impact of the tool on the clinician–patient interaction before clinical studies. It may therefore offer a useful and important environment in the early testing of new technological tools. The present results will inform further tool development and clinician training materials.
We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors—arousal and attention—via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.
Two wild oat (Avena fatua L.) biotypes and two barley (Hordeum vulgare L.) varieties known to have intraspecific differential response to foliarly-applied 4-chloro-2-butynyl m-chlorocarbanilate (barban) were studied. When barban was applied to the roots, the intraspecific differential response (measured by shoot retardation) was maintained in both species but to a much lesser extent than previously observed with foliar application. Wild oat maintained a greater differential response than barley. Therefore, the factors causing the differential response to foliarly-applied barban may reside primarily in the leaves of both species but to some extent elsewhere (perhaps at the plant apex) in the wild oat biotypes and to a lesser extent elsewhere in the barley varieties. Differential response to foliar applications was not caused by differential uptake, but may be caused primarily by the susceptible biotype or variety's reduced ability to degrade barban beyond 3-chloroaniline. This might cause the greater build-up of compound X (a water-soluble 3-chloroaniline-containing metabolite of barban) observed in the susceptible biotype or variety. Compound X appeared to be nonphytotoxic. The build-up of compound X in turn may reduce the rate of metabolism of barban resulting in the greater amount of free barban found in the treated leaf of the susceptible biotype or variety 12 to 24 hr after treatment. This greater amount of free barban in the leaf of the susceptible biotype or variety may be responsible for the differential response to foliar applications of barban. Evidence for this partial explanation of the differential response was better for barley than for wild oat.
We evaluated 214 lines of wild oat (Avena fatua L.) for response to S-2,3-dichloroallyl N,N-diisopropylthiolcarbamate (diallate), S-2,3,3-trichloroaHyl N,N-diisopropylthiolcarbamate (triallate), and 4-chloro-2-butynl m-chlorocarbanilate (barban). We found large differences among the lines in response to these herbicides and some lines that might not be controlled by recommended rates of these herbicides. Frequency distributions of response to herbicides suggest that reaction to these three herbicides is quantitatively inherited. We were unable to establish a relationship between morphological characteristics and plant response to these herbicides.
Before paediatric cardiology emerged as a specialty in the mid 20th century, a body of literature had developed over centuries devoted to description of congenitally malformed hearts. In this review, we have selected highlights from such texts written during the period of 100 years from 1814 to 1914, demonstrating their potential relevance to controversies occurring during the twentieth century in the categorisation of such hearts. We begin in 1814, with the first wide-ranging book devoted to congenital cardiac malformations. We end with a publication from 1914, because it included an illustration of the first electrocardiogram in a text devoted to paediatric disease. As we will show, these works from the 19th and early 20th centuries reflect topics still relevant today, namely the aetiology of cardiac malformations, clinicopathologic correlations, attempts at classification, and lack of effective treatments. Attention to their content could have served to ameliorate controversies, some of them ongoing.
Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4 % (w/w) fish oil (n 19) or 4 % (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10·6 (sd1·2)), parietal (10·2 (sd1·5)) and occipital brain lobes (9·9 (sd 1·3)), but not in the temporal lobe (7·7 (sd1·6)), compared with pigs fed the HOSF diet (frontal lobe, 7·5 (sd1·0); parietal lobe, 8·1 (sd 1·3); occipital lobe, 7·3 (sd1·2), temporal lobe, 6·6 (sd1·2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.
Dynamic friction, wear volumes and wear morphology have been studied for sliding wear in polysilicon in ambient air at μN normal loads using on-chip micron-scale test specimens. With increasing number of wear cycles, the friction coefficients show two distinct types of behavior: (i) an increase by a factor of two and a half to a steady-state regime after peaking at three times the initial value of about 0.10 ± 0.04, with no failure after millions of cycles; (ii) an increase by a factor larger than three followed by failure after ∼105 cycles. Additionally, the average nano-scale wear coefficient sharply increased in the first ∼105 cycles up to about 10−4 and then decayed by an order of magnitude over the course of several million cycles. For both modes of behavior, abrasive wear is the governing mechanism, the difference being attributed to variations in the local surface morphology (and wear debris) between the sliding surfaces. The oxidation of worn polysilicon surfaces only affects the friction coefficient after periods of inactivity (>30 min).
Fetal bradycardia may herald fetal demise. This article highlights arrhythmic fetal bradycardia rather than bradycardia caused by perinatal distress. We briefly examine the embryonic conduction system's development and physiology and we review the classification, aetiology, evaluation, and approach to fetal bradycardia. Our aim is to provide the clinician with practical information about fetal bradycardia that enlightens causative conditions and aids management.